Phase 2 Study of HKI-272 in Subjects with Advanced Breast Cancer

Phase 1

Conditions: Breast cancer is the most frequently diagnosed malignancy and the second most common cause of cancer related deaths in women. HER2 is a member of the epidermal growth factor receptor (EGFR) family that includes EGFR/HER1, HER2, HER3 and HER4, all being receptor tyrosine-protein kinases. The oncogenic role of HER2 has been extensively documented in breast cancer, where it is overexpressed in 25% to 30% of breast cancers.

Registration Number: EUCTR2005-003098-26-FR

Lead Sponsor: Wyeth Research Division of Wyeth Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 122

Inclusion Criteria

1.Pathologic diagnosis of breast cancer and current stage IIIB, IIIC, or IV breast cancer not curable with available therapy.
2.Progression following at least six weeks of standard doses of Herceptin (trastuzumab) or a Herceptin containing regimen. (Arm A only)
3.Tumor tissue available and adequate for HER2 gene amplification
4.HER2 gene amplified tumor by FISH (fluorescence in situ hybridization)
5.At least 1 measurable lesion as defined by modified RECIST criteria.
6.Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 (not declining within past 2 weeks)
7.Women aged >= 18 years
8.Life expectancy of at least 12 weeks
9.Screening laboratory values within the following parameters: ANC>= 1.5 x 109/L (1,500/mm3) Platelet count>= 75 x 109/L (75,000/mm3) Hemoglobin >= 9.0 g/dL (80g/L) Serum creatinine <= 1.5 x upper limit of normal (ULN) Total bilirubin<= 1.5 x ULN AST and ALT<= 2.5 x ULN (<= 5 x ULN if liver metastases are present)
10.For women of child bearing potential, a negative serum pregnancy test result before study entry. A woman of child bearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or are using contraceptives.
11.Willingness of female subjects, who are not surgically sterile or postmenopausal, to use medically acceptable methods of birth control for the duration of the study and for 28 days after the last dose of test article.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Prior treatment with Herceptin or any HER2-targeted treatment (Arm B only)
2.More than 2 prior cytotoxic chemotherapy treatment regimens for relapsed or metastatic disease.
3.Major surgery, chemotherapy, radiotherapy, investigational agents or other cancer therapy within 1 week of treatment day 1.
4.Extensive visceral disease including bilateral diffuse lymphangitic involvement of the lung with more than 50% lung involvement, extensive hepatic involvement defined as involvement of more than one third of the liver confirmed by CT or MRI scan.
5.Subjects with bone or skin as the only site of measurable disease
6.Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (subjects with a history of CNS metastases or cord compression are allowable if they have been definitively treated and are clinically stable for at least 4 weeks before first dose of test article). 7.History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association [NYHA] functional classification of >3), angina, myocardial infarction, or ventricular arrhythmia.
8.Left ventricular ejection fraction less than 50% measured by multigated blood pool imaging of the heart (MUGA) scanning or echocardiogram (ECHO)
9.QTc interval > 0.47 second
10.Prior treatment with anthracyclines with a cumulative dose of doxorubicin or equivalent > 400 mg/m2
11.Pregnant or breast feeding women
12.Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (e.g, Crohn’s disease, malabsorption, or Grade >=2 diarrhea of any etiology at baseline)
13.Inability or unwillingness to swallow the HKI-272 capsules
14.Evidence of significant medical illness or abnormal laboratory finding that would, in the investigator’s judgment, make the subject inappropriate for this study. Examples include, but are not limited to, serious active infection (i.e. requiring intravenous antibiotic or antiviral agent), uncontrolled major seizure disorder, any other active malignancy (except for breast cancer).